tbuckley/cabot-search huggingface dataset:
Abstract 12901: Cardiac Reverse Remodeling and Functional Changes Assessed by Speckle Tracking Echocardiography After Septal Myectomy in Patients With Symptomatic Hypertrophic Obstructive Cardiomyopathy
Authors: Kyungeun Ha, Hee Jeong Lee, Seo-Yeon Gwak, Kyu Kim, Kyu-Yong Ko, Geu-Ru Hong, Jong-Won Ha, Chi Y Shim
Journal: Circulation (2022)

Introduction &amp; Hypothesis: Surgical septal myectomy is an effective treatment in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM). Reducing the hemodynamic burden through septal myectomy in HOCM patients is expected to result in cardiac reverse remodeling, but it is unknown whether it improves myocardium functional parameters, which are proven prognosticators for clinical outcome. Therefore, this study aimed to investigate the left atrial (LA) and left ventricular (LV) size and function using conventional and speckle tracking echocardiography (STE) before and after septal myectomy in patients with HOCM. Methods: A total of 65 patients with symptomatic HOCM who underwent surgical septal myectomy from 2006 to 2021 were retrospectively analyzed. Patients were excluded if they underwent a valve repair or replacement at the same time. Finally, clinical, echocardiographic, and electrocardiographic variables before and after the surgery were comprehensively analyzed. Results: After septal myectomy, there were significant decreases in LA volume index (72±22 vs. 57±18 ml/m 2 , p &lt;0.001) suggestive of improvement of diastolic function. In the analysis of STE, there was no significant difference in LA strain (19.3±8.5 vs. 19.1±8.2%, p=0.883) and LV global longitudinal strain (LS) (-10.3±3.6 vs. -9.6±3.4%, p=0.150) before and after septal myectomy. When we analyzed LV regional LS by dividing into septum and non-septum, septal LS showed a little aggravation (-8.7±4.5 vs. -7.6±3.7 %, p=0.077) with marginal statistical significance. In addition, non-septal LS was not significantly different after septal myectomy (-10.9±4.5 vs. -10.5 ±4.2 %, p= 0.458). The change of LA volume index was significantly correlated with change of QRS duration. Interestingly, the septal LS was deteriorated and non-septal LS tended to be improved as widening of QRS duration. Conclusions: After septal myectomy, as hemodynamic load due to LVOT obstruction relieves, there is a significant reduction in LA volume. However, there is no improvement in the global LA and LV mechanical function. Widening of QRS duration, a marker of effective septal myectomy, is associated with LA volume reduction and improvement of longitudinal strain in non-septal LV.
Abstract 13133: Effect of Ocedurenone in Patients With Uncontrolled Hypertension and Stage 3b/4 Chronic Kidney Disease - Subgroup Analysis of a Phase 2b Clinical Trial
Authors: June Ye, James McCabe, Vincent Benn, Y Fred F YANG, Judy Tan, Jinrong Liu, George L Bakris, Bertram Pitt
Journal: Circulation (2022)

Introduction: BLOCK-CKD is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety, efficacy, and pharmacokinetics of the nonsteroidal MRA Ocedurenone (KBP-5074) in patients with stage 3b/4 CKD and uncontrolled hypertension while taking 2 or more antihypertensive medications. Hypothesis: Although the study is not powered for subgroup analysis, it is of interest to examine the consistency of results across various subgroups. Methods: Of 162 patients randomized, 138 (85.2%) completed the study. Effect of Ocedurenone on SBP reduction and serum potassium levels by baseline eGFR &lt; 30, eGFR ≥ 30, and diabetic status was explored. Results: Consistent and clinically meaningful SBP reduction at Day 84 was observed in the subgroups analyzed. SBP mean (SE) change from baseline to day 84 in the eGFR &lt; 30 group were 0.2 (3.03), -12.7 (5.45), and -15.4 (5.01) for placebo, 0.25mg, and 0.5mg doses respectively. In the ≥ 30 group, the changes were -9.7 (3.38), -10.8 (3.29), and -16.1 (4.08), respectively. In the diabetic patient group, the changes were -4.2 (4.22), -11.8 (5.91), and -13.0 (6.5) respectively. In the non-diabetic patient group, the changes were -6.0 (2.93), -11.4 (3.34), and -17.1 (3.51) respectively. Similar small dose-dependent increases in serum potassium were observed in nearly all subpopulations. Changes from baseline to day 84 in SBP by baseline eGFR and diabetic status and the corresponding changes in serum potassium and eGFR by baseline eGFR and diabetic status are shown in Figure 1. Conclusions: In this Phase 2 trial, the effect of Ocedurenone on SBP reduction and serum potassium levels was consistent among clinically important subgroups. Due to the relatively small number of patients these conclusions need to be confirmed in the larger ongoing Phase 3 trial.
Abstract 14412: Statin Use and Incident Heart Failure by Race and Cardiovascular Disease Risk in a Real World Primary Prevention Cohort
Authors: Eli J Hay, Jianhui Zhu, Floyd W Thoma, Oscar C MARROQUIN, Pallavi Muluk, Amber E Johnson, Malamo E Countouris, Anson J Smith, Gul J Saeed, Mahmoud Al Rifai, Anum Saeed, Suresh R Mulukutla
Journal: Circulation (2022)

Background: Statins are indicated for primary prevention in patients with elevated risk of atherosclerotic CVD (ASCVD). However, statin associated risk reduction in heart failure (HF) is uncertain. There remain racial disparities in statin prescription and associated ASCVD outcomes. We evaluated the association of statin therapy and incident HF stratified by race and estimated ASCVD risk in a primary prevention cohort. Methods: Statin use in Black and White patients without ASCVD and HF was evaluated (2013-2019) based on the ACC/AHA 10y risk groups ( Borderline [5%-7.4%], Intermediate [7.5-19.9%], or High [≥20%]). Guideline Directed Statin Intensity (GDSI) was defined as “at least moderate” for intermediate and high risk patients. Statin use and HF outcome was assessed via electronic health care record and ICD-10 codes. Cox regression models, fully adjusted for CVD risk factors, were used to calculate HRs for the association between statin use and incident HF. Results: In 270,079 patients, 39% Black and 32% White patients were categorized as intermediate or high ASCVD risk. Proportionally fewer Black patients in intermediate (22% vs. 31%) and high (40% vs. 44%) risk groups received "any statin" (all p&lt;0.001). At 6y follow up, incident rate of HF was 12.9 per 1000-person-y in those with highest ASCVD risk. Black patients had higher risk of HF events [(HR HF 1.11 (1.05-1.17), p&lt;0.001)]. In both populations, high risk patients not on any statin had significantly higher risk of HF [(HR HF 1.42 (1.04-1.93) in Black and 1.22(1.08-1.37) in White] ( Table ). The interaction between race and statin use was not a significant predictor of incident HF. Conclusion: In a large healthcare system, statin use was low among White and Black patients. Lack of statin therapy was associated with a higher risk of incident HF amongst those at highest ASCVD risk. Further research is needed to study the role of statins in primary prevention of HF, especially in higher risk populations.
Abstract 12824: Predictive Value of Artificial Intelligence-Enabled Electrocardiography in Patients with Takotsubo Cardiomyopathy
Authors: Yoshihisa Kanaji, Ilke Ozcan, David N Tryon, Ali Ahmad, Jaskanwal D Sara, Tsunekazu Kakuta, Lilach O Lerman, Zachi Attia, Amir Lerman
Journal: Circulation (2022)

Introduction: Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TTC). This study sought to evaluate the prognostic value of our institutional artificial intelligence-augmented electrocardiography (AI-ECG) algorithms in patients with TTC. Methods: This study enrolled consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry. TTC was diagnosed according to the Mayo Clinic diagnostic. Our clinic’s previously developed and validated AI-ECG algorithms were used for detection of ECG-Age, probability of low ejection fraction, and probability of atrial fibrillation.Multivariable models were constructed to evaluate the association of AI-ECG and other clinical characteristics with major adverse cardiac events (MACE), defined as cardiac death, recurrence of TTC, nonfatal myocardial infarction, hospitalization for congestive heart failure, and stroke. Results: In the final analysis, 305 patients were studied over a median follow-up of 4.8 years. Patients with MACE were more likely to be older, have history of hypertension and chronic heart failure (CHF), worse renal function as well as having high-risk AI-ECG findings compared to those without. In the multivariate Cox proportional hazard analysis, the presence of 3 or 4 high-risk findings detected by AI-ECG, remained a significant predictor of MACE in the patients with TTC after adjusted by conventional risk factors (hazard ratio (HR) 2.17, 95% CI [1.33, 3.53], P=0.002; HR 2.44, 95% CI [1.38, 4.29], P=0.002, respectively). Conclusions: The combined use of developed AI-ECG algorithms derived from a single 12-lead ECG might identify ECG correlates of underlying non-transient myocardial dysfunction and detect subtle underlying patterns associated with worse outcomes in patients with TTC. This approach might be beneficial for stratifying high-risk patients with TTC.
Abstract 129: A Systemic Proteomics Analysis Identifies Energy Generation Pathways That Characterize The Vulnerability Of Brain And Kidney As Compared To Heart And Liver After Cardiac Arrest
Authors: Muhammad Shoaib, Jin-woong Choi, Kei Hayashida, Rishabh Choudhary, Santiago Miyara, Seunguk J Baek, Patricia M Curtin, Lance B Becker, Ju Yeon Lee, Junhwan Kim
Journal: Circulation (2022)

Background: Substantial organ dysfunction and dynamically altered physiology is observed after whole-body ischemia-reperfusion injury resulting from cardiac arrest (CA) and resuscitation. There are limited therapeutic interventions available because this disease process is complex, and the pathophysiology is poorly understood. By understanding the dynamic alterations in the proteome of the brain, heart, kidney, and liver following CA and resuscitation, we can better characterize the underlying disease mechanisms in order to identify novel therapeutic targets. Methods: Male Sprague-Dawley rats underwent 20 min asphyxial-CA and resuscitation via cardiopulmonary bypass. Brain, heart, kidney, and liver tissues were harvested post-CA or post-resuscitation. Protein levels in these tissues were analyzed by cutting-edge proteomics analysis. We then performed a thorough bioinformatics analysis at the organ, organelle, and pathway levels to assess the pathologic state of each organ following CA and resuscitation. Results: The total number of proteins identified and quantified were 3411, 1928, 2731, and 2879 in the brain, heart, kidney, and liver, respectively. Statistical analysis revealed that the brain and liver showed more significant overall alterations than the heart and kidney after CA. Resuscitation significantly normalized the proteomic alterations in the heart and liver but not in the brain and kidney. Among many essential metabolic pathways altered, such as amino acid biosynthesis or lipid metabolism, proteins that participate in oxidative phosphorylation, the key energy generating pathway, were substantially altered in the brain and kidney. Furthermore, proteins related to glycolysis, another major energy generating pathway, were also significantly altered in the brain. Conclusions: The differential proteome alteration after global ischemia-reperfusion post-CA and resuscitation emphasizes the vulnerability of brain and kidney in their failure to restore energy generating pathways in contrast with the resilience of heart and liver. The novel informatics analysis provides mechanistic insights into the pathologic state of major organs and provides potential therapeutic targets to improve outcomes after CA.
Abstract 148: No Bystander Cardiopulmonary Resuscitation For Out-Of-Hospital Cardiac Arrest In Vietnam: Impact On The Outcomes
Authors: Son N Do, Chinh Q Luong, Toshie Manabe, My H Nguyen, Dung T Pham, Tra T Ton, Quoc T Hoang, Dat T Nguyen, Thao T Pham, Hanh T Hoang, Dai Q Khuong, Quan H Nguyen, Tuan A Nguyen, Hien D Dang, Hai B Hoang, Chi V Nguyen, Anh D Nguyen, Bryan F McNally, Marcus E Ong, Co X Dao
Journal: Circulation (2022)

Introduction: Bystander CPR is not often performed on OHCA patients, particularly in limited-resource regions. This study aimed to investigate the rate of OHCA patients who did not receive bystander CPR and its impact on the outcomes in an LMIC. Hypothesis: Understanding the reasons bystanders are reluctant to call EMS and how no bystander CPR impacts the outcomes of OHCA patients are crucial for improving survival in Vietnam. Methods: We performed a multicenter prospective cohort study of OHCA patients (≥18 years) presenting to three central hospitals in Vietnam from February 2014 to December 2018. We collected data on characteristics, management, and outcomes and compared these data between patients who did not receive bystander CPR and patients who did. Using logistic regression, we assessed factors associated with survival and good neurological function on discharge (a CPC score of 1 or 2). Results: Of 521 patients, 388 (74.5%) were male, and the mean age was 56.71 years (SD: 17.32). Although most cardiac arrests (68.7%; 358/521) occurred at home and 67.9% (353/520) were witnessed by bystanders, a high rate (77.9%, 406/521) of these patients did not receive bystander CPR. Only half of the patients were taken by EMS (8.1%, 42/521) or private ambulance (42.8%, 223/521); 50.8% (133/262) of whom were given resuscitation attempts by EMS or private ambulance. There was no significant difference in survival to admission (16.7%; 68/406 and 24.3%; 28/115; p=0.064) and survival to discharge (7.9%; 32/406 and 14.8%; 17/115; p=0.094) between patients who did not receive bystander CPR and patients who did. In contrast, the rate of good neurological function of patients who did not receive bystander CPR (4.7%, 19/406) was significantly lower than that of patients who received bystander CPR (12.2%, 14/115; p=0.004). Moreover, multivariate analysis showed that no bystander CPR (OR: 0.276; 95% CI: 0.124-0.614) was inversely and independently associated with good neurological function. Conclusions: In our study, poor outcomes emphasize the need for increasing bystander CPR performance, increasing the number of EMS ambulances and the utilization of private ambulances, and developing a standard emergency first-aid program for both healthcare personnel and the community.
Abstract 12874: A Novel Mechanism in the Pathogenesis of Heart Failure With Preserved Ejection Fraction Through Hexokinase Mitochondrial Dislocation and Substrate Shuttling Into the O-Glcnacylation Machinery
Authors: Yuki Tatekoshi, Jason S Shapiro, Mingyang Liu, George M Bianco, Farzaneh Sharifzad, Adam De Jesus, Navid Koleini, Andrew Wasserstrom, Hossein Ardehali
Journal: Circulation (2022)

Introduction: Endothelial cell (EC) dysfunction underlies the pathogenesis of heart failure with preserved ejection fraction (HFpEF), however, the mechanism is unclear. ECs are highly dependent on glycolysis; however, it is not known how their metabolic profile is altered in the setting of HFpEF. Hexokinase 1 (HK1) carries the first step in glycolysis and is mostly bound to the mitochondria in ECs. Objective: We sought to elucidate the role of EC glucose metabolism, and specifically HK1, in the development of HFpEF. Results: We first showed that among glycolytic enzymes, HK1 is highly specific to ECs, suggesting the significance of HK1 in EC physiology. Although HK1 mRNA and protein levels are not changed, we noted increased dislocation of HK1 from the mitochondria in ECs from HFpEF mice. To study the role of HK1 dislocation in the development of HFpEF, we generated mice with mitochondrial-binding domain of the endogenous HK1 replaced with Flag tag (ΔE1HK1). ΔE1HK1mice develop impaired cardiac relaxation at 20 weeks of age and HFpEF by 40 weeks, and ECs from these mice displayed impaired angiogenic potential. Since HK1 is involved in glucose metabolism, we then performed metabolomic studies and demonstrated that intermediates in hexosamine biosynthetic pathway (HBP) are significantly decreased in ECs from ΔE1HK1 mice. To assess the mechanism for the decrease in HBP, we assessed protein modification, and noted reduced protein N-glycosylation and increased O-GlcNAcylation in ECs from ΔE1HK1. We also demonstrated that inhibition of the key enzyme in O-GlcNAcylation (OGT) reverses the EC dysfunction noted in ΔE1HK1 mice, indicating that O-GlcNAcylation is responsible for the angiogenic defect in ECs from ΔE1HK1. Finally, to provide a mechanism for altered protein glycosylation with HK1 mitochondrial dislocation, we showed that HK1 associates with N-glycosylation machinery when it is attached to mitochondria, while it binds to OGT when it is dislocated from mitochondria. Conclusion: Our studies demonstrate a role for HK1 mitochondrial binding and protein O-GlcNAcylation in the pathogenesis of HFpEF, and that HK1 cellular localization plays a major role in the fate of HBP intermediates into either N-glycosylation or O-GlcNAcylation machinery in ECs.
Abstract 14852: Association Between Features of Adverse Myocardial Function Beyond Ejection Fraction and Outcomes in Heart Failure With Preserved Ejection Fraction
Authors: Anthony Peters, Robert M Clare, Karen Chiswell, Michael Felker, Anita M Kelsey, Robert J Mentz, Adam D Devore
Journal: Circulation (2022)

Background: Heart failure (HF) guidelines recommend assessment of left ventricular ejection fraction (LVEF) to classify patients and guide therapy implementation. However, LVEF alone may be insufficient to adequately characterize patients with HF with mildly reduced or preserved LVEF. Recommendations on additional testing are lacking, and echocardiographic features beyond LVEF are relatively under-investigated in the real-world HFpEF population despite their ubiquity in clinical practice. Methods: Using an echocardiographic and clinical database from a large US healthcare system, patients with HFpEF were defined as those with LVEF&gt;40% and at least one distinct billing diagnosis of acute or chronic HF. The association of the following metrics with mortality was evaluated: global longitudinal strain (GLS&gt;-16), left atrial volume (LAVi&gt;28), left ventricular hypertrophy (LVH), and E/e’&gt;13 &amp; e’&lt;9. A multivariable model for mortality was constructed including age, sex, and key co-morbidities followed by stepwise selection of echocardiographic features. Results: Among 2,337 patients with complete echocardiographic data, the following features were associated with all-cause mortality over 3 years of follow-up: E/e’ + e’, GLS, LAVi (all p&lt;0.01). In the multivariable model (c-index=0.65), only GLS was independently associated with all-cause mortality (HR 1.35 [1.11-1.63], p=0.002). In the setting of normal LVEF (&gt;55%), 498 patients (39.7%) demonstrated decreased GLS. This cohort demonstrated higher event rates compared to patients with normal GLS irrespective of LVEF ( Figure, Panel A-B ). Conclusions: In a large, real-world HFpEF population, echocardiographic features of HFpEF, led by GLS, are associated with adverse outcomes irrespective of LVEF. A large subset of patients demonstrate adverse myocardial function by GLS despite preserved LVEF and may represent a key cohort of interest for therapy implementation and future clinical studies.
Abstract 13515: LDL-Cholesterol, Coronary Plaque, and Resilience to Coronary Atherosclerosis in a Middle-Aged Asymptomatic US Population: The Miami Heart Study at Baptist Health South Florida
Authors: Kobina Hagan, Miguel Cainzos Achirica, Reed Mszar, Shozab S Ali, Lara Arias, Anshul Saxena, Ricardo C Cury, Matthew Budoff, Theodore Feldman, Shubham Lahan, Michael J Blaha, Michael D Shapiro, Garima Sharma, Raul D Santos, Jonathan Fialkow, Khurram Nasir
Journal: Circulation (2022)

Introduction: The interplay between LDL-C and coronary plaque has not been described in contemporary, asymptomatic US cohorts undergoing CCTA assessment. Also, the prevalence of resilience to coronary atherosclerosis despite high LDL-C in the general primary prevention population is poorly understood. Methods: Cross-sectional analysis using data from the ongoing, prospective Miami Heart Study. Descriptive statistics were computed among statin-naïve participants by LDL-C levels (&lt;70, 70-100, 100-130, 130-160, 160-190, ≥190 mg/dL) and a combined group of statin-naïve with LDL-C≥190 and statin users with LDL-C≥130 (“high LDL-C”). Study outcomes included CAC=0 vs &gt;0, any plaque on CCTA, maximal stenosis ≥50%, and ≥1 and ≥2 high-risk plaque features. Logistic regression models evaluated associations between LDL-C and the outcomes, adjusting for other risk factors. Results: The demographics and outcomes of 1,808 participants not on statin are summarized in the Table by LDL-C levels. Higher LDL-C levels were strongly and independently associated with CAC&gt;0 (fully adjusted OR for LDL≥190 vs &lt;70 mg/dL: 2.62, 95%CI 1.04, 6.60) and had a marginally significant association with any plaque (fully adjusted OR: 2.26, 95%CI 0.95, 5.37). However, among participants with LDL-C≥190, 54% had CAC=0, and 40% no plaque. Similar numbers were observed among participants with “high LDL-C” (N=159), in which 45% had CAC=0 and 35% no plaque. Among those with high LDL-C and CAC=0, approximately 28% had non-calcified plaque on CCTA, although the prevalence of high-risk plaque findings was very low. Conclusions: LDL-C is strongly associated with coronary atherosclerosis. However, in this cohort (mean age 53 years; 54% women), CAC=0 and the absence of coronary plaque were frequent findings among individuals with high LDL-C. These observations may be used to inform more personalized paradigms in ASCVD risk assessment and in the allocation of novel LDL-C-lowering therapies in this group.
Abstract 13169: Cardiac Arrest and Severe Arterial Vasospasm in a 37-Year-Old Woman With Recent Covid Infection
Authors: Sam Dow, Christopher Lee, Merle Myerson
Journal: Circulation (2022)

CASE: A 37-year-old woman with history of smoking, hypertension and mild COVID-19 diagnosed 40 days prior with intermittent chest pain since then presented to the emergency department (ED) via EMS for an out-of-hospital ventricular fibrillation cardiac arrest. She was resuscitated at home with a downtime of 15 minutes. Her initial ED EKG was normal and she was admitted to the cardiac ICU. Shortly after admission she developed a junctional rhythm with ST elevation in lead II followed by polymorphic ventricular tachycardia which degenerated into ventricular defibrillation. She received 3 shocks with subsequent resuscitation. She was started on an amiodarone drip and underwent coronary angiography. With right femoral artery engagement she was noted to have severe vasospasm. An initial angiogram of the left coronary system showed mild coronary disease, subsequent injection showed diffuse vasospasm in the entire left coronary system. Telemetry showed diffuse ST elevations and QT widening with injections followed by ventricular fibrillation treated with 8 counter-shocks and the addition of lidocaine. An intra-aortic balloon pump was placed prior to transfer back to the ICU. She was initially treated with nicardipine and transitioned to amlodipine for treatment of vasospasm. Rheumatologic work-up was unremarkable and she underwent placement of an ICD for secondary prevention. A Coronary CT was performed in follow-up showing only minimal luminal irregularities with no RCA disease. DISCUSSION: COVID-19 has been linked to many cardiovascular abnormalities including diffuse vasospasm with acute infection. This is the first case describing diffuse vasospasm in a person who is in the post-COVID period which is defined as greater than 4 weeks after diagnosis. This case provides information on severe arterial vasospasm seen in the time period after acute COVID infection indicating that follow up after COVID for any cardiovascular abnormalities is needed.